Thymic size and T-cell function decrease with age, and it has not yet been possible to totally reverse this thymic atrophy and completely restore T-cell-dependent immune functions. In this study, GH3 pituitary adenoma cells, which secrete growth hormone and prolactin, were implanted subcutaneously into 16-and 22-month-old female Wistar-Furth rats and the rats were sacrificed approximately 2 months later. Only thymic remnants were detected in aged, non-implanted rats, but thymus glands were found in both the 18-and the 24-month-old rats that had been implanted with GH3 cells. Thymus glands from the GH3-implanted 18-month-old rats contained distinct cortical thymocytes and medullary epithelial cells. Depending on the concentration of phytohemagglutinin or concanavalin A, T-cell proliferative responses of splenocytes from these implanted rats were 2-to 5-fold greater than those of 18-month-old controls. At the optimal concentration of mitogen, proliferative responses to either lectin could be restored to those levels observed in splenocytes from 3-monthold Wistar-Furth females. Thymus glands from 24-month-old GH3-implanted rats contained more cortical thymocytes and fewer fat vacuoles than controls, but they were not totally reconstituted. No significant lectin-induced T-cell proliferative responses or IL-2 secretion were detected in 24-month-old control rats, but splenocytes from GH3-implanted rats showed augmented T-cell proliferative responses and increased synthesis of IL-2. Fluorescence-activated cell-sorter analysis of thymocytes revealed that 24-month-old rats implanted with GH3 cells had a higher proportion of lymphocytes with the Thy-1.1 and helper-T-cell phenotypes. These data show that it is possible to regenerate normal thymic tissue in situ and reverse the natural loss in cell-mediated immunity that occurs with aging.

The effects of vitamin A and beta-carotene on various reproductive parameters were examined in 108 crossbred gilts. Gilts were fed a diet free of vitamin A and beta-carotene for 5 wk, then assigned to one of eight treatments. Statistical comparisons were performed on three sub-groupings of these treatments as follows: (1) DEFICIENT (received 2,100 IU of vitamin A X head-1 X d-1, (2) FED (received dietary supplementation of 0, 2,100 or 12,300 IU vitamin A and (or) 0, 32.6 or 65.2 mg beta-carotene X head-1 X d-1) or (3) INJECTED (received injection supplementation of 0 or 12,300 IU vitamin A and 32.6 mg beta-carotene X head-1 X d-1, administered once weekly). Gilts remained on treatment through weaning of litters at 21 d postpartum. Plasma vitamin A and beta-carotene levels were greatly elevated in INJECTED gilts. Concentrations of these compounds in plasma were similar between DEFICIENT and FED gilts. There was no treatment difference in number of corpora lutea/gilt. Embryonic mortality was lowest (P less than .01 to .02) in INJECTED gilts (14 +/- 3%) compared with DEFICIENT (29 +/- 5%) or FED (25 +/- 3%) gilts. Baby pig mortality averaged 6 +/- 1% and was not different among treatments. INJECTED gilts had more (P less than .05 to .01) piglets/litter at birth and at weaning (9.5 +/- .3 and 9.0 +/- .3 piglets/litter, respectively) than DEFICIENT (7.9 +/- .5 and 7.6 +/- .5 piglets/litter) or FED gilts (8.7 +/- .3 and 8.1 +/- .3 piglets/litter).(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone (GH) appears to play a major role in a reciprocal axis that has been postulated between the thymus and pituitary glands. Our previous studies showed that thymic structure, as well as T-cell proliferation and IL-2 synthesis, could be restored in aged female Wistar-Furth rats by the implantation of GH3 pituitary adenoma cells. These cells secrete GH and some prolactin. We have now used three different approaches to determine whether GH affects a variety of immune events in vivo in both old and young rodents, and whether GH3 cells can directly affect progenitor T-cells in nude rats that congenitally lack a thymus gland. To test the effects of GH in aged rats, 750 micrograms of pituitary-derived ovine GH was injected 2 x daily into 26-month-old Fischer 344 rats for 5 weeks. This approach demonstrated that GH augments splenocyte proliferation to T-cell lectins as well as natural killer (NK) activity at low effector:target ratios even though morphologic characteristics of the thymus were not altered. To assess the effect of GH in young rodents, mice were studied that were transgenic for the rat metallothionein-GH gene. Histologic evaluation of thymus glands revealed that the amount of adipose tissue and the number of epithelial cells and Hassall's corpuscles are augmented in transgenic mice. Splenocyte proliferation at suboptimal mitogen doses is greater in transgenic than in control littermate mice, but neither IL-2 synthesis nor antibody synthesis to sheep erythrocytes is affected. The role of pituitary hormones on progenitor T-cells was then explored by implanting GH3 cells into Rowett nude rats.(ABSTRACT TRUNCATED AT 250 WORDS)

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